Hypercalcemia

Hypercalcemia

 

Hypercalcemia is a common metabolic abnormality which is frequently related to primary hyperparathyroidism.

Epidemiology

  • Incidence – 8/100,000
  • Age – average is 55 years; range is 40-60 years
  • Sex – F>M for primary hyperparathyroidism

Etiology

  • Primary hyperparathyroidism
  • Malignancy
    • Usually metastatic disease; 1/3 related to squamous cell carcinoma
  • Humoral mediated parathyroid related peptide cancer
  • Excess vitamin D or rarely vitamin A
  • Milk-alkali syndrome
  • Elevated vitamin D, 1, 25-dihydroxy  (granulomatous disease and B- and T-cell lymphomas)

Risk Factors

  • Genetic
    • Multiple Endocrine Neoplasia (MEN)
      • MEN 1 (Werner Syndrome)
        • Hyperparathyroidism, tumors of the anterior pituitary and enterohepatic tumors such as Zollinger-Ellison
      • MEN 2A
        • Medullary carcinoma of the thyroid, pheochromocytoma and mild hyperparathyroidism
    • Familial hypocalciuric hypercalcemia
      • Hypercalcemia with subnormal urine calcium excretion
      • Removal of parathyroids does not correct hypocalcemia
    • Neonatal severe primary hyperparathyroidism
      • Rare, potentially lethal
      • Enlargement of all 4 parathyroids with very high parathyroid hormone (PTH)
    • Hyperparathyroidism – jaw tumor syndrome
      • Hyperparathyroidism with cementoossifying tumors of the jaw, Wilms tumor and renal cysts

Pathophysiology

  • Hyperparathyroidism
    • Four parathyroid glands found within the thyroid gland secrete PTH
    • PTH acts directly on bone and induces calcium resorption with a tight negative feedback loop
    • Pathology
      • Adenoma
      • Hyperplasia
      • Carcinoma (rare)
    • Most patients are asymptomatic when hypercalcemia is discovered due to frequent use of screening chemistries

Clinical Presentation

  • Clinical symptoms progress slowly
    • Renal – nephrolithiasis
    • Cancer – usually fatigue, weakness as a result of very high calcium levels
    • Bone – classic finding is osteitis fibrosa which is rare
    • Central nervous system – easy fatigability, proximal muscle weakness, muscle atrophy
    • Gastrointestinal – vague symptoms of nausea, bloating, constipation

Diagnosis

  • Laboratory testing
    • Indicated when hypercalcemia detected; measure ionized serum calcium
    • Intact PTH

Differential Diagnosis

  • Metastatic cancer
  • Medication induced (eg, thiazide diuretics)
  • Immobilization
  • Granulomatous disease (sarcoidosis, TB)
  • Vitamin D intoxication
  • Paget disease

Treatment

  • Based on etiology of hypercalcemia

See Also